Acetaminophen overdose is common and can result from deliberate/nonstaggered or accidental/staggered ingestion. Patients presenting within 24 h of an acetaminophen overdose can safely be managed on medical wards. Early management of nonstaggered overdose is guided by the plasma acetaminophen concentration, whereas management of accidental/staggered ingestion is guided by ingested dose. Ingested dose and time from ingestion to presentation are important prognostic factors in accidental/staggered ingestion. Acetaminophen-induced acute liver failure (ALF) requires meticulous supportive care in an intensive care unit (ICU), with early identification and transfer of patients who are likely to require liver transplantation to a specialist liver centre. The modified King's College Hospital criteria (incorporating lactate into the traditional criteria) represent the best tool for identifying patients who require transplantation.